Uro-genital conditions or diseases commonly affect both men and women. These conditions include infections and/or inflammation of the urinary system and the genital system. For example, according to the National Institute of Child Health and Human Development (NICHD), “most women will have at least one form of vaginitis in their lifetime.”Vaginitis, National Institute of Child Health and Human Development—Publications On-line, www.nichd.nih.giv/publications/pubs/vag1.htm. The causes for vaginitis range from bacterial, fungal or viral infections to irritations from chemicals in creams, sprays, or even clothing that are in contact with this area. Id. For women with bacterial and fungal infections, these infectious agents often originate from the rectal area and migrate across the perineum to reach the vagina or the urethra.
A common type of vaginitis is candidiasis or yeast infection that is most commonly caused by Candida albicans. The Candida species are part of an individual's normal flora of microbial organisms present in skin, mouth, and the gastrointestinal tract. Robbins Pathologic Basis of Disease 5th ed., Saunders Co., Philadelphia (1994) p. 354. They also live in small numbers in a woman's vagina. They grow best in warm, moist surfaces such as the vagina or the oral cavity. They are normally non-pathogenic, but when a change in their environment occurs, such as in response to a woman's hormonal changes in menopause, pregnancy, or in response to stress, they can overgrow to cause a yeast infection. These changes can also occur in immunosuppressed or compromised individuals such as people undergoing chemotherapy, taking immunosuppresants, or afflicted with AIDS.
Current treatment for candidiasis includes over the counter drugs with active ingredients such as butoconazole nitrate (Femstat®), clotrimazole (Gyne-Lotrimin® and others), miconazole (Monistat® and others), and tioconazole (Vagistat®). These drugs are topically applied in the vagina and break down Candida's cell wall. Other similar treatments include prescription drugs with active ingredients in the same family such as fluconazole (Diflucan®), terconazole (Terazol®), and ketoconazole (Nizoral®).
Although vaginitis has been commonly associated with Candida, bacterial vaginosis is actually the most common vaginal infection in women of reproductive age according to the NICHD. Vaginitis, supra. Overgrowing of bacteria in the vagina causes bacterial vaginosis much like Candida, but the drugs used for its treatment are different.
On the other hand, men can also contract Candida infections on their penis involving the glans and the prepuce. Balanoposthitis, a nonspecific infection of the glans and prepuce, is caused by a wide variety of organisms including fungi such as Candida and pyogenic bacteria such as Staphylococci Sp. Robbins Pathologic Basis of Disease 5th ed., Saunders Co., Philadelphia (1994), p. 1008.
Staphylococci are gram positive bacteria that are normally present in skin and other mucosal membranes of the body. Staphylococcus aureus, in particular, is a virulent pathogen that causes a myriad of conditions and diseases stemming from skin lesions, endocarditis, respiratory infection, food poisoning and toxic shock syndrome.
For women using highly absorbent tampons, it is known that S. aureus can colonize the vagina and secrete a toxin called toxic shock syndrome toxin (TSST-1). According to the Food and Drug Administration, approximately half of the toxic shock syndrome cases reported today are associated with tampon use during menstruation and usually in young women. Tampons and Asbestos, Dioxin, & Toxic Shock Syndrome, FDA Center for Devices and Radiological Health (Jul. 23, 1999), www.fda.gov/cdrh/ocd/tamponsabs.html.
S. aureus infections are commonly treated with methicillin. Although it is very effective, some strains of S. aureus have developed resistance to methicillin, and only a few antibiotics can successfully treat methicillin-resistant Staphylococcus aureus (MRSA) infections. One of these antibiotics commonly used for MRSA is vancomycin. A strain of S. aureus, however, with reduced susceptibility to vancomycin (VISA) has already been identified. Khurshid, M. A., et. al., Staphylococcus aureus with Reduced Susceptibility to Vancomycin—Illinois, 1999, Morbidity and Mortality Weekly Report, 48(51): 1165-1167 (2000), www.cdc.gov/epo/mmwr/preview/mmwrhtml/mm4851a1.htm. The emergence of antibiotic resistant bacterial strains has created a need for alternative ways to combat bacterial infections.
In addition to infection by fungi and bacteria, viral vaginitis is also common. These infections are most often transmitted through sexual intercourse. Viral vaginitis includes infection by herpes simplex virus (HSV) or human papillomavirus (HPV). HSV viruses, for example, replicate in the genital area, which is the site of entrance, and also infect the neurons that innervate the genitals. To avoid the body's immune system, HSV viruses can remain latent in these neurons, and become reactivated in response to environmental conditions such as stress, immunosuppression, irradiation, or viral infection. Current treatments for HSV include drugs such as acyclovir, famciclovir, or valacyclovir.
As for the urinary system, according to the American Medical Association, urinary tract infections (UTIs) are one of the most common disorders prompting a physician visit. Women's Health, Urinary Tract Infections: A Patient's Guide to Treatment, AMA Health Insight, On-Line Health Information for Everyone, www.ama-assn.org/insight/h_focus/wom_hlth/uti/uti.htm. These infections are most often caused by Escherichia coli, but can also involve organisms such as Candida Sp. and Staphylococci Sp. Id. These infections can start at the urethra and travel up to the bladder causing cystitis. Ultimately, it can even ascend to the kidneys through the ureters and cause pyelonephritis. Both men's and women's urinary systems can become infected with these microorganisms.
Since uro-genital conditions are not confined to one single cause, current treatments require different drugs to treat specific causes. These causes have to be first identified. Identification requires time, but more so, requires a gynecological examination for women to determine the specific infectious agents or lack thereof.
With the increased use of antibiotics and other drugs, microorganisms, such as methicillin-resistant Staphylococcus aureus, are increasingly developing resistance to currently available drugs. Thus, a continuing need exists for new classes of drugs that can combat the broad spectrum of infectious agents. It has been discovered that dimers comprising Lysine-Proline-Valine as well as other alpha-MSH based peptides disclosed herein, are effective in treating urogenital conditions.